| 1. |
- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 2. |
- Hannan, Katherine M., et al.
(författare)
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Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 41:5
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Tidskriftsartikel (refereegranskat)abstract
- The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
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| 3. |
- Hein, Tobias, 1982, et al.
(författare)
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Can minimal running shoes imitate barefoot heel-toe running patterns? A comparison of lower leg kinematics
- 2014
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Ingår i: Journal of Sport and Health Science. - : Elsevier BV. - 2095-2546. ; 3:2, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous studies about the interaction between footwear (and barefoot) and kinematic and kinetic outcomes have been published over the last few years. Recent studies however lead to the conclusion that the assumed interactions depend mainly on the subjects' experience of barefoot (BF) walking/running, the preferred running strike pattern, the speed, the hardness of the surface, the thickness of the midsole material, and the runners' level of ability. The aim of the present study was to investigate lower leg kinematics of BF running and running in minimal running shoes (MRS) to assess comparability of BF kinematics in both conditions. To systematically compare both conditions we monitored the influencing variables described above in our measurement setup. We hypothesized that running in MRS does not alter lower leg kinematics compared to BF running. Methods: Thirty-seven subjects, injury-free and active in sports, ran BF on an EVA foam runway, and also ran shod wearing Nike Free 3.0 on a tartan indoor track. Lower-leg 3D kinematics was measured to quantify rearfoot and ankle movements. Skin markers were used in both shod and BF running. Results: All runners revealed rearfoot strike pattern when running barefoot. Differences between BF and MRS running occurred particularly during the initial stance phase of running, both in the sagittal and the frontal planes. BF running revealed a flatter foot placement, a more plantar flexed ankle joint and less inverted rearfoot at touchdown compared to MRS running. Conclusion: BF running does not change the landing automatically to forefoot running, especially after a systematic exclusion of surface and other influencing factors. The Nike Free 3.0 mimics some BF features. Nevertheless, changes in design of the Nike Free should be considered in order to mimic BF movement even more closely. Copyright (C) 2014, Shanghai University of Sport. Production and hosting by Elsevier B. V. All rights reserved.
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| 4. |
- Hein, Tobias, 1982, et al.
(författare)
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Prospective analysis of intrinsic and extrinsic risk factors on the development of Achilles tendon pain in runners
- 2014
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 24:3
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Tidskriftsartikel (refereegranskat)abstract
- There are currently no generally accepted, consistent results that clearly characterize factors causing Achilles tendon pain (AT) in runners. Therefore, we carried out a prospective study to evaluate the multifactorial influence of clinical, biomechanical (isometric strength measurements and three-dimensional kinematics) and training-related risk factors on the development of AT. Two hundred sixty-nine uninjured runners were recruited and underwent an initial examination. One hundred forty-two subjects completed their participation by submitting training information on a weekly basis over a maximal period of 1 year. Forty-five subjects developed an overuse injury, with 10 runners suffering from AT. In an uninjured state, AT runners already demonstrated decreased knee flexor strength and abnormal lower leg kinematics (sagittal knee and ankle joint) compared with a matched control group. A relationship between years of running experience or previous overuse injuries and the development of new symptoms could not be established. The interrelationship of biomechanical and training-specific variables on the generation of AT is evident. A combination of alterations in lower leg kinematics and higher impacts caused by fast training sessions might lead to excessive stress on the Achilles tendon during weight bearing and thus to AT in recreational runners.
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| 5. |
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| 6. |
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| 7. |
- Jungmalm, Jonatan, 1991, et al.
(författare)
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Associations between biomechanical and clinical/anthropometrical factors and running-related injuries among recreational runners: a 52-week prospective cohort study.
- 2020
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Ingår i: Injury epidemiology. - : Springer Science and Business Media LLC. - 2197-1714. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this exploratory study was to investigate whether runners with certain biomechanical or clinical/anthropometrical characteristics sustain more running-related injuries than runners with other biomechanical or clinical/anthropometrical characteristics.The study was designed as a prospective cohort with 52-weeks follow-up. A total of 224 injury-free, recreational runners were recruited from the Gothenburg Half Marathon and tested at baseline. The primary exposure variables were biomechanical and clinical/anthropometrical measures, including strength, lower extremity kinematics, joint range of motion, muscle flexibility, and trigger points. The primary outcome measure was any running-related injury diagnosed by a medical practitioner. Cumulative risk difference was used as measure of association. A shared frailty approach was used with legs as the unit of interest. A total of 448 legs were included in the analyses.The cumulative injury incidence proportion for legs was 29.0% (95%CI=24.0%; 34.8%). A few biomechanical and clinical/anthropometrical factors influence the number of running-related injuries sustained in recreational runners. Runners with a late timing of maximal eversion sustained 20.7% (95%CI=1.3; 40.0) more injuries, and runners with weak abductors in relation to adductors sustained 17.3% (95%CI=0.8; 33.7) more injuries, compared with the corresponding reference group.More injuries are likely to occur in runners with late timing of maximal eversion or weak hip abductors in relation to hip adductors.
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| 8. |
- Koska, Daniel, 1986, et al.
(författare)
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Validation of an inertial measurement unit for the quantification of rearfoot kinematics during running
- 2018
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Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362. ; 64, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: The popular protocol used to study running motion suffers from problems that lead to a limited ability to generalize the obtained results. Inertial measurement units (IMU) appear to be promising in increasing ecological validity of the collected data. However, quantifying running kinematics utilizing IMU signals is complex and potentially affected by several well-established and less well-known errors. Research question: The purpose of this study was to examine the validity of kinematic variables obtained from a single, shoe-mounted IMU using an opto-electronic motion analysis reference system. Methods: 51 recreational runners were analyzed, performing a single continuous run at three different speeds (10, 12, 15 km/h) on a treadmill. Descriptive statistics (Bland & Altman analysis, box plots, scatter plots) were employed to analyze the agreement between the two instruments. Results: The findings of this study revealed considerable systematic and large random disagreement, which, in turn, is characterized by substantial inter-individual differences in the error distribution. These discrepancies may partly be explained by differences in foot strike behavior, resulting in varying degrees of vibration impact acting on the IMU. Significance: Advances in IMU technology, as well as exploring new application approaches and signal processing strategies, might enhance the usability of IMUs in analyzing running kinematics.
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| 9. |
- Linz, Dominik, et al.
(författare)
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Longer and better lives for patients with atrial fibrillation : the 9th AFNET/EHRA consensus conference
- 2024
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 26:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA).Methods and results: Eighty-three international experts met in Munster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF.Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF. Graphical Abstract
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| 10. |
- Lundby, Carsten, et al.
(författare)
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Physiological, biochemical, anthropometric, and biomechanical influences on exercise economy in humans
- 2017
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 0905-7188. ; 27:12, s. 1627-1637
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Tidskriftsartikel (refereegranskat)abstract
- Interindividual variation in running and cycling exercise economy (EE) remains unexplained although studied for more than a century. This study is the first to comprehensively evaluate the importance of biochemical, structural, physiological, anthropometric, and biomechanical influences on running and cycling EE within a single study. In 22 healthy males (VO(2)max range 45.5-72.1mLmin-1kg-1), no factor related to skeletal muscle structure (% slow-twitch fiber content, number of capillaries per fiber), mitochondrial properties (volume density, oxidative capacity, or mitochondrial efficiency), or protein content (UCP3 and MFN2 expression) explained variation in cycling and running EE among subjects. In contrast, biomechanical variables related to vertical displacement correlated well with running EE, but were not significant when taking body weight into account. Thus, running EE and body weight were correlated (R-2=.94; P<.001), but was lower for cycling EE (R-2=.23; P<.023). To separate biomechanical determinants of running EE, we contrasted individual running and cycling EE considering that during cycle ergometer exercise, the biomechanical influence on EE would be small because of the fixed movement pattern. Differences in cycling and running exercise protocols, for example, related to biomechanics, play however only a secondary role in determining EE. There was no evidence for an impact of structural or functional skeletal muscle variables on EE. Body weight was the main determinant of EE explaining 94% of variance in running EE, although more than 50% of the variability of cycling EE remains unexplained.
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